Journal
JOURNAL OF NEUROCHEMISTRY
Volume 93, Issue 1, Pages 118-127Publisher
WILEY
DOI: 10.1111/j.1471-4159.2004.02993.x
Keywords
Alzheimer's disease; beta-amyloid; cytotoxicity; heparin-binding domain; reactive oxygen species; vascular endothelial growth factor
Categories
Ask authors/readers for more resources
beta-amyloid (A beta) is a major component of senile plaques that is commonly found in the brain of Alzheimer's disease (AD) patient. In the previous report, we showed that an important angiogenic factor, vascular endothelial growth factor (VEGF) interacts with A beta and is accumulated in the senile plaques of AD patients' brains. Here we show that A beta interacts with VEGF(165) isoform, but not with VEGF(121). A beta binds to the heparin-binding domain (HBD) of VEGF(165) with similar affinity as that of intact VEGF(165). A beta binds mostly to the C-terminal subdomain of HBD, but with greatly reduced affinity than HBD. Therefore, the full length of HBD appears to be required for maximal binding of A beta. Although A beta binds to heparin-binding sequence of VEGF, it does not bind to other heparin-binding growth factors except midkine. Thus it seems that A beta recognizes unique structural features of VEGF HBD. VEGF(165) prevents aggregation of A beta through its HBD. We localized the core VEGF binding site of Ab at around 26-35 region of the peptide. VEGF(165) and HBD protect PC12 cells from the A beta-induced cytotoxicity. The mechanism of protection appears to be inhibition of both A beta-induced formation of reactive oxygen species and A beta aggregation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available